Notch signaling inhibition induces G0/G1 arrest in murine Leydig cells

Andrologia. 2019 Nov;51(10):e13413. doi: 10.1111/and.13413. Epub 2019 Sep 15.

Abstract

As a highly evolutionarily conserved signaling pathway, Notch widely participates in cell-fate decisions and the development of various tissues and organs. In male reproduction, research on the Notch signaling pathway has mainly concentrated on germ cells and Sertoli cells. Leydig cells are the primary producers of testosterone and play important roles in spermatogenesis and maintaining secondary sexual characteristics. In this study, we used TM3 cells, a murine adult Leydig cell line, to investigate the expression profiles of Notch receptors and ligands and observe the effect of Notch signaling on the proliferation of TM3 cells. We found that Notch 1-3 and the ligands Dll-1 and Dll-4 were expressed in TM3 cells, Notch 1-3 and the ligand Dll-1 were expressed in testis interstitial Leydig cells, and Notch signaling inhibition suppressed the proliferation of TM3 cells and induced G0/G1 arrest. Inhibition of Notch signaling increased the expression of p21Waf1/Cip1 and p27. Overall, our results suggest that Notch inhibition suppresses the proliferation of TM3 cells and P21Waf1/Cip1 , and p27 may contribute to this process.

Keywords: Leydig cell; P21Waf1/Cip1; P27; cell proliferation.

MeSH terms

  • Animals
  • Benzene Derivatives / pharmacology*
  • Cell Line
  • Cell Proliferation / drug effects
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • G1 Phase Cell Cycle Checkpoints / drug effects*
  • Leydig Cells / drug effects*
  • Leydig Cells / physiology
  • Male
  • Mice
  • Propionates / pharmacology*
  • Receptors, Notch / antagonists & inhibitors*
  • Receptors, Notch / metabolism
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology
  • Sulfones / pharmacology*

Substances

  • 3-(4-((4-chlorophenyl)sulfonyl)-4-(2,5-difluorophenyl)cyclohexyl)propanoic acid
  • Benzene Derivatives
  • Cdkn1a protein, mouse
  • Cdkn1b protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • Propionates
  • Receptors, Notch
  • Sulfones
  • Cyclin-Dependent Kinase Inhibitor p27